Metformin for Exercise Capacity

Overseen By Emily E Grammer, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Virginia

Must not be taking: Metformin, Insulin, GLP-1, SGLT-2

Disqualifiers: Type 1 or 2 diabetes, Smoking, Severe liver or kidney disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 19 days

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether metformin, a common diabetes medication, affects exercise performance. Researchers aim to determine if metformin alters exercise capacity, potentially making it more difficult. Participants will take metformin and a placebo (a pill with no active drug) while undergoing exercise tests, body scans, and tracking their diet and symptoms. The trial seeks recreationally active adults who have not taken metformin before and exercise at least three times a week. As a Phase 4 trial, metformin is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial requires that participants do not use medications that significantly alter glucose regulation, such as metformin, insulin, or similar drugs. If you are taking any of these, you would need to stop before participating.

What is the safety track record for metformin?

Research has shown that metformin is generally safe for use. It is a common medication for managing type 2 diabetes and is usually well-tolerated.

One study found that metformin did not affect exercise test results, such as oxygen consumption or exercise duration. However, it lowered heart rate and made exercise feel more challenging. Another study suggested that metformin might reduce some fitness benefits of exercise by affecting muscle changes.

Despite these effects on exercise response, metformin remains safe for people with type 2 diabetes to use alongside exercise. Its long history of use and strong safety record support this conclusion. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using metformin for enhancing exercise capacity because it offers a unique approach compared to existing options like lifestyle changes or other pharmacological aids. Metformin, traditionally used as a diabetes medication, is being explored for its potential to improve muscle metabolism and endurance. While most treatments for boosting exercise performance focus on direct endurance training or nutritional supplements, metformin works differently by potentially enhancing the body's energy utilization at the cellular level. This could mean improved exercise capacity without the need for extensive training or dietary adjustments, offering a promising alternative for those looking to boost their fitness more efficiently.

What evidence suggests that metformin might alter exercise capacity?

This trial will compare the effects of Metformin with a placebo on exercise capacity. Research has shown that Metformin, a common drug for type 2 diabetes, might affect exercise performance. Some studies suggest that Metformin can reduce the usual benefits of exercise, such as improving fitness. A review of several studies found that while Metformin did not change overall exercise test results, it made exercise feel slightly harder. Additionally, Metformin reduced the positive effects of exercise on fitness levels. These findings suggest that although Metformin effectively controls blood sugar, it might not be ideal for those aiming to enhance exercise performance. ^{1 3 4 6 7}

Who Is on the Research Team?

Jason Allen, PhD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for healthy, active adults aged 18-30 who have never taken Metformin, with a BMI under 30. Women must be premenopausal with regular menstrual cycles and all participants should be able to follow the study schedule.

Inclusion Criteria

I exercise at least 3 days a week.

I am willing and able to follow the study's schedule and procedures.

I have never taken Metformin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants undergo a 19-day treatment phase with metformin and placebo, including exercise tests and body composition assessments

19 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview

The study tests whether Metformin affects exercise capacity in young adults. Participants will take both Metformin and a placebo at different times, complete bike exercises, body composition tests, and keep track of their food intake and any symptoms.

How Is the Trial Designed?

Group I: Metformin (MET) Experimental Treatment 1 Intervention

At the end of the screening visit, participants will be randomized to either Condition A or Condition B (MET or PL first). Participants will begin the 19-day treatment phase of study the day after screening. During each treatment phase, participants will consume metformin as follows: 1x500 mg tablet/day for 5 days, 2x500 mg tablets/day for 5 days, and 3x500 mg tablets/day (or maximally tolerated dosage) for 9 days. Participants will then complete a VO2peak/LT test on day 16, rest for 48 hours, then complete a time-to-exhaustion test (day 19) during the final days of the treatment phase. After the time-to-exhaustion test, participants will begin the placebo treatment phase.

Group II: Placebo (PL) Placebo Group 1 Intervention

At the end of the screening visit, participants will be randomized to either Condition A or Condition B (MET or PL first). Participants will begin the 19-day treatment phase of study the day after screening. During each treatment phase, participants will consume placebo as follows: 1x500 mg tablet/day for 5 days, 2x500 mg tablets/day for 5 days, and 3x500 mg tablets/day (or maximally tolerated dosage) for 9 days. Participants will then complete a VO2peak/LT test on day 16, rest for 48 hours, then complete a time-to-exhaustion test (day 19) during the final days of the treatment phase. After the time-to-exhaustion test, participants will begin the metformin treatment phase.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

Metformin extended release (ER) provides effective glycaemic control with once-daily dosing, showing similar effectiveness to twice-daily dosing of immediate-release formulations over a 24-week period in clinical trials.

The metformin ER formulation was well tolerated at doses of 1500 and 2000 mg/day, with no increase in adverse events, indicating its safety for patients managing their blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin extended release for the treatment of type 2 diabetes mellitus. Schwartz, SL., Wu, JF., Berner, B.[2019]

Glumetz (M-ER) is a newly approved extended-release formulation of metformin that provides effective and sustained glycemic control with once-daily dosing, showing similar bioavailability to immediate-release metformin taken twice daily.

In clinical trials lasting 24 weeks, M-ER demonstrated good efficacy and was well tolerated, with continued glycemic control maintained in an additional 24-week open-label extension study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of metformin extended-release tablets for type 2 diabetes: an overview. Schwartz, SL., Gordi, T., Hou, E., et al.[2013]

In a study involving healthy rats, Metformin (Met) did not enhance the benefits of exercise on physical performance, indicating it may not improve exercise outcomes despite its common use in diabetes management.

However, Metformin was found to protect muscle cells from damage caused by exercise and positively influence muscle adaptation, suggesting its potential therapeutic role in conditions where muscle function is impaired.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Protects Rat Skeletal Muscle from Physical Exercise-Induced Injury. Abbadessa, G., Maniscalco, E., Grasso, L., et al.[2023]

In a study involving 251 participants with type 2 diabetes, metformin users showed a significant reduction in HbA1c levels after aerobic training compared to control, while non-users did not show this benefit.

Metformin did not negatively impact changes in fitness, body weight, or waist circumference resulting from exercise, suggesting it does not hinder the positive effects of exercise on glycaemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does metformin modify the effect on glycaemic control of aerobic exercise, resistance exercise or both? Boulé, NG., Kenny, GP., Larose, J., et al.[2022]

In a study involving 15 healthy males, metformin (MET) increased the rate of perceived exertion (RPE) during fixed-intensity exercise, indicating that participants felt they were working harder when on MET compared to a placebo.

However, MET did not significantly reduce self-selected exercise intensity, as measured by oxygen consumption rate, suggesting that while it may affect perceived effort, it does not limit the intensity at which individuals choose to exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Metformin on Self-Selected Exercise Intensity in Healthy, Lean Males: A Randomized, Crossover, Counterbalanced Trial. Pilmark, NS., Petersen-Bønding, C., Holm, NFR., et al.[2022]

In a study involving 90 individuals with overweight/obesity and prediabetes, metformin treatment did not lead to a reduction in free-living physical activity levels over 13 weeks, indicating that it does not negatively impact daily activity.

Despite increased perceived exertion during exercise on metformin, the treatment did not affect overall physical activity or sedentary behavior compared to a control group or those treated with dapagliflozin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of metformin treatment on volumes of free-living physical activity and sedentary behaviour: A post-hoc analysis of the PRE-D trial. Karstoft, K., Ried-Larsen, M., Bruhn, L., et al.[2023]

Chronic intake of metformin in healthy rats significantly increased anaerobic work capacity (AWC - W') and time until exhaustion during high-intensity swimming, indicating improved performance in anaerobic activities.

However, metformin did not affect aerobic capacity, as there was no difference in critical load (CL) between the metformin and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic metformin intake improves anaerobic but not aerobic capacity in healthy rats. de Araujo, GG., Learsi, S., Bastos-Silva, VJ., et al.[2020]

In a systematic review of studies involving 388 participants, metformin did not significantly change overall oxygen consumption (VO2) or peak oxygen consumption (VO2peak), indicating it may not enhance exercise capacity in the general population.

However, metformin was associated with a significant decrease in heart rate and respiratory exchange ratio, along with an increase in perceived exertion during exercise, suggesting it may alter exercise response without improving performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of metformin on exercise capacity: A meta-analysis. Das, S., Behera, SK., Srinivasan, A., et al.[2018]

In a study involving seven healthy swimmers, metformin intake (500 mg) was found to increase the anticipation of blood lactate peak concentration during high-intensity swimming intervals, suggesting a potential metabolic efficiency benefit.

However, metformin did not significantly affect neuromuscular responses, perceived exertion, or overall swimming performance, indicating that while it may influence certain metabolic parameters, it does not enhance athletic performance in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin anticipates peak of lactate during high-intensity interval training but no changes performance or neuromuscular response in amateur swimmers. Norberto, MS., De Arruda, TB., Cursiol, JA., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3120188/

Metformin and Exercise in Type 2 Diabetes

By increasing heart rate, metformin could lead to the prescription of lower exercise workloads. Furthermore, under the tested conditions, exercise interfered ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0168822718310064

Effect of metformin on exercise capacity: A meta-analysis

In the overall population, metformin did not affect VO2, VO2peak, exercise test duration and VAT, although it significantly decreased HR, RER and increased RPE.

3.

news-medical.net

news-medical.net/news/20251107/Diabetes-drug-blunts-exercise-induced-health-improvements.aspx

Diabetes drug blunts exercise-induced health improvements

But when metformin was added, the improvements shrank. The drug also diminished gains in aerobic fitness and reduced the positive effects on ...

4.

frontiersin.org

frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.599164/full

The Effect of Metformin on Self-Selected Exercise Intensity ...

Self-selected exercise intensity was not reduced by MET in healthy males, despite the fact that MET increased RPE during an exercise bout with fixed intensity.

5.

rutgers.edu

rutgers.edu/news/why-your-daily-walk-might-not-work-well-if-youre-metformin

Why Your Daily Walk Might Not Work as Well if You're on ...

But when metformin was added, the improvements shrank. The drug also diminished gains in aerobic fitness and reduced the positive effects on ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6351883/

Metformin inhibits mitochondrial adaptations to aerobic ...

Metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle ...

7.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/69/NCT03355469/Prot_SAP_002.pdf

Exercise Dose and Metformin for Vascular Health in Adults ...

The overarching hypothesis is that metformin may blunt adaptation following high intensity exercise by lowering/attenuating oxidative stress ...